import pandas as pd
pd.set_option("display.max_columns", None)
import plotly.io as pio
import plotly.express as px # Plotting
pio.renderers.default = 'notebook'
pd.options.plotting.backend = "plotly"
from tqdm import tqdm
from pprint import pprint
tqdm.pandas()
df = pd.read_csv("applications.csv")
df.Community_URL__c = "https://connect.pharmac.govt.nz" + df.Community_URL__c
df

events = pd.read_json(f"applications/{df['Id'].iloc[0]}.json").dropna()
events

days_until_each_stage = pd.to_datetime(events.set_index("name").dateString.dropna(), errors="coerce").diff().dropna()
days_until_each_stage.index = "Days until " + days_until_each_stage.index
days_until_each_stage

/tmp/ipykernel_997791/985086398.py:1: UserWarning:

Could not infer format, so each element will be parsed individually, falling back to `dateutil`. To ensure parsing is consistent and as-expected, please specify a format.

name
Days until Seeking Clinical Advice            31 days
Days until Under Assessment                  181 days
Days until Options Compared                  458 days
Days until Under Consultation                122 days
Days until Reviewing Consultation Feedback    31 days
Days until Decision                          212 days
Name: dateString, dtype: timedelta64[ns]

pprint(events.events.iloc[-1])

[{'Event_Description': {'change': None,
                        'fs': 'The funding application has been declined.',
                        's': 'The funding application has been declined.'},
  'Formatted_Date': {'change': None, 'fs': 'Jun 2025', 's': 'Jun 2025'},
  'Links': {'change': None,
            'fs': '<p><a '
                  'href="https://www.pharmac.govt.nz/news-and-resources/consultations-and-decisions/2025-06-decision-to-decline-inactive-applications-for-the-funding-of-some-medicines" '
                  'target="_blank">Notification of the decision</a></p>',
            's': '<p><a '
                 'href="https://www.pharmac.govt.nz/news-and-resources/consultations-and-decisions/2025-06-decision-to-decline-inactive-applications-for-the-funding-of-some-medicines" '
                 'target="_blank">Notification of the decision</a></p>'},
  'Outcome': {'change': None, 'fs': None, 's': None},
  'PTAC_Comments': {'change': None, 'fs': None, 's': None},
  'Published_Application': {'change': None, 'fs': None, 's': None},
  'Published_Discussion': {'change': None, 'fs': None, 's': None},
  'Published_Recommendation': {'change': None, 'fs': None, 's': None},
  'Summary': {'change': None, 'fs': None, 's': None},
  'change': None,
  'e': {'Event_Date__c': '2025-06-17',
        'Event_Description__c': 'The funding application has been declined.',
        'Formatted_Date__c': 'Jun 2025',
        'Id': 'a0POZ00000Mc77I2AR',
        'Links__c': '<p><a '
                    'href="https://www.pharmac.govt.nz/news-and-resources/consultations-and-decisions/2025-06-decision-to-decline-inactive-applications-for-the-funding-of-some-medicines" '
                    'target="_blank">Notification of the decision</a></p>',
        'Stage__c': 'Decision',
        'Status_History__c': 'a13OZ00000OhRFMYA3',
        'attributes': {'type': 'Application_Event__c',
                       'url': '/services/data/v65.0/sobjects/Application_Event__c/a0POZ00000Mc77I2AR'}}}]

rows = []
for i, row in tqdm(df.iterrows(), total=len(df)):
    events = pd.read_json(f"applications/{row.Id}.json").dropna()
    start = pd.to_datetime(events.events.iloc[0][0]["e"]["Event_Date__c"])
    end = pd.to_datetime(events.events.iloc[-1][0]["e"]["Event_Date__c"])
    delta = end - start
    row = row.to_dict()
    row["Application Received date"] = start
    row["Last Update date"] = end
    row["Days elapsed between application and last update"] = delta.days
    days_until_each_stage = pd.to_datetime(events.set_index("name").dateString.dropna(), errors="coerce", format="%b %Y").diff().dropna()
    days_until_each_stage.index = "Days until " + days_until_each_stage.index
    row.update(days_until_each_stage)
    for stage in events.events:
        stage_events = []
        for event in stage:
            try:
                stage_events.append(event["e"]["Event_Date__c"] + ":" + event["e"]["Event_Description__c"])
            except KeyError:
                print(event)
        row[event["e"]["Stage__c"] + " dates"] = "\r\n".join(stage_events)
    rows.append(row)

df = pd.DataFrame(rows)
df.sort_values("Application Received date", inplace=True)
df

 16%|█▌        | 320/2015 [00:01<00:05, 291.03it/s]

{'Summary': {'s': None, 'fs': None, 'change': None}, 'Published_Recommendation': {'s': None, 'fs': None, 'change': None}, 'Published_Discussion': {'s': None, 'fs': None, 'change': None}, 'Published_Application': {'s': None, 'fs': None, 'change': None}, 'PTAC_Comments': {'s': None, 'fs': None, 'change': None}, 'Outcome': {'s': None, 'fs': None, 'change': None}, 'Links': {'s': None, 'fs': None, 'change': None}, 'Formatted_Date': {'s': 'Jul 2012', 'fs': 'Jul 2012', 'change': None}, 'Event_Description': {'s': None, 'fs': None, 'change': None}, 'e': {'attributes': {'type': 'Application_Event__c', 'url': '/services/data/v65.0/sobjects/Application_Event__c/a0POZ000000vYNw2AM'}, 'Id': 'a0POZ000000vYNw2AM', 'Event_Date__c': '2012-07-01', 'Stage__c': 'Under Assessment', 'Formatted_Date__c': 'Jul 2012', 'Status_History__c': 'a132P000000Aq3yQAC'}, 'change': None}

 42%|████▏     | 851/2015 [00:03<00:04, 274.40it/s]

{'Summary': {'s': None, 'fs': None, 'change': None}, 'Published_Recommendation': {'s': None, 'fs': None, 'change': None}, 'Published_Discussion': {'s': None, 'fs': None, 'change': None}, 'Published_Application': {'s': None, 'fs': None, 'change': None}, 'PTAC_Comments': {'s': None, 'fs': None, 'change': None}, 'Outcome': {'s': None, 'fs': None, 'change': None}, 'Links': {'s': None, 'fs': None, 'change': None}, 'Formatted_Date': {'s': 'Dec', 'fs': 'Dec', 'change': None}, 'Event_Description': {'s': 'Public consultation for this application is now closed. Pharmac is reviewing consultation feedback.', 'fs': 'Public consultation for this application is now closed. Pharmac is reviewing consultation feedback.', 'change': None}, 'e': {'attributes': {'type': 'Application_Event__c', 'url': '/services/data/v65.0/sobjects/Application_Event__c/a0P2P000007JyAAUA0'}, 'Id': 'a0P2P000007JyAAUA0', 'Event_Description__c': 'Public consultation for this application is now closed. Pharmac is reviewing consultation feedback.', 'Stage__c': 'Reviewing Consultation Feedback', 'Formatted_Date__c': 'Dec', 'Status_History__c': 'a132P000000Clc2QAC'}, 'change': None}

 55%|█████▌    | 1111/2015 [00:03<00:03, 274.33it/s]

{'Summary': {'s': None, 'fs': None, 'change': None}, 'Published_Recommendation': {'s': None, 'fs': None, 'change': None}, 'Published_Discussion': {'s': None, 'fs': None, 'change': None}, 'Published_Application': {'s': None, 'fs': None, 'change': None}, 'PTAC_Comments': {'s': None, 'fs': None, 'change': None}, 'Outcome': {'s': None, 'fs': None, 'change': None}, 'Links': {'s': None, 'fs': None, 'change': None}, 'Formatted_Date': {'s': 'Aug 2022', 'fs': 'Aug 2022', 'change': None}, 'Event_Description': {'s': None, 'fs': None, 'change': None}, 'e': {'attributes': {'type': 'Application_Event__c', 'url': '/services/data/v65.0/sobjects/Application_Event__c/a0POZ0000012oZf2AI'}, 'Id': 'a0POZ0000012oZf2AI', 'Event_Date__c': '2022-08-01', 'Stage__c': 'Seeking Clinical Advice', 'Formatted_Date__c': 'Aug 2022', 'Status_History__c': 'a132P000000DwrGQAS'}, 'change': None}

 72%|███████▏  | 1448/2015 [00:05<00:02, 267.97it/s]

{'Summary': {'s': None, 'fs': None, 'change': None}, 'Published_Recommendation': {'s': '<p>The Committee recommended the new formulation and device of adalimumab be listed on the Pharmaceutical Schedule if cost-neutral to the existing presentations of adalimumab, including the future costs of adalimumab with regards to patent extension and the introduction of biosimilar presentations.</p><p><br></p><p>The Committee took into account, where applicable, PHARMAC&#39;s relevant decision-making framework for these recommendations.</p>', 'fs': '<p>The Committee recommended the new formulation and device of adalimumab be listed on the Pharmaceutical Schedule if cost-neutral to the existing presentations of adalimumab, including the future costs of adalimumab with regards to patent extension and the introduction of biosimilar presentations.</p><p><br></p><p>The Committee took into account, where applicable, PHARMAC&#39;s relevant decision-making framework for these recommendations.</p>', 'change': None}, 'Published_Discussion': {'s': '<p>The Committee noted that adalimumab 10 mg, 20 mg and 40 mg subcutaneous presentations are currently listed on Pharmaceutical Schedule, subject to a Special Authority for a range of conditions. The Committee noted that some patients experience significant pain associated with the subcutaneous injection of adalimumab with the currently listed product, however these patients are receiving treatment for chronic conditions that are associated with ongoing pain and the benefit of treatment would usually outweigh the short-term injection related pain.</p><p><br></p><p>Members noted that adalimumab appears to be a more painful injection than etanercept, however only a small number of patients report that injection associated pain was the reason they switched to another injectable biologic (Navarro-Millán et al. PLoS ONE 2016;11(3):e0149781).</p><p><br></p><p>The Committee noted that the new presentation incorporates a two-fold change to the presentation of adalimumab (Humira) to create a citrate-free (CF) formulation, in order to reduce the injection volume, and changes the auto-injector pen device and needle size to aid administration. The current formulation and device could remain available until 30 June 2019 (the end of AbbVie’s current subsidy and delisting protection), although it would be the supplier’s preference to replace the current product sooner. Members noted there may be a potential stock risk in the future if New Zealand continues to list a product that is different to other countries and that PHARMAC staff would need to assess this risk.</p><p><br></p><p>The Committee noted the supplier submitted a new medicine application to Medsafe for the new 40 mg/0.4 ml formulation in March 2016 and registration is expected by May 2017. Members noted that registration of the 10 mg and 20 mg products is not expected until the end of 2018 and these strengths would continue to be available as pre-filled syringes only.</p><p><br></p><p>The Committee noted weak evidence that citrate buffers may be associated with increased pain on subcutaneous injection in comparison with alternatives such as histidine buffer or normal saline (Larsen et al. Basic &amp; Clinical Pharmacology &amp; Toxicology 2006; 98:218–21).\xa0</p><p><br></p><p>Members noted increased injection volume is also associated with increased pain. However, Members considered both concentrations of adalimumab are in a relatively small volume (0.4 ml and 0.8ml). A study by Heise et al. (Diabetes, Obesity and Metabolism 2014;16:971–6) suggested that there may be little difference in pain on injection of either 0.4 or 0.8 ml volume. The Committee considered that it is unclear if a change in needle gauge from 29 to 27 would significantly affect pain on injection.</p><p><br></p><p>The Committee noted four studies provided in the application regarding pain on injection (M10-867, M11-964, M12-783, and M12-159). Two studies were relatively large Phase I trials (M10-867, M12-159) where pre-filled syringes were used to administer a single dose of one of the formulations to healthy subjects. Members noted the Visual Analogue Scale (VAS) scores immediately after injection were statistically significantly higher in the users of the original formulation. However, there was significant variation between subjects as indicated by a very large standard deviation in the numeric results. Pain had diminished significantly by 15 minutes in both treatment arms. Results for both Phase I studies were similar. </p><p><br></p><p>Members noted that two Phase II trials (M11-964 and M12-783) evaluated injection pain following use of a pre-filled syringe of either the current or high-concentration formulation, in treatment naïve and pain experienced patients who had received at least 6 consecutive adalimumab doses prior to screening. Members noted that a recently published paper (Nash et al. Rheumatol Ther August 2016, published online DOI 10.1007/s40744-016-0041-3) provides more detail regarding the VAS scores and shows a statistical difference in VAS immediately after injection between the two formulations. Of note, there is a large numerical difference in scores between the two studies. However, the authors have no explanation for this. Members noted that 67% of patients in the pooled population experienced greater than or equal to 1.3cm less pain following receipt of the 40mg/0.4ml versus the 40mg/0.8ml formulation (p&lt;0.001) and the mean difference in immediate pain after injection for the pooled population was -2.48 (95% CI -2.97 to -2.00; p&lt;0.001). Members noted the minimum clinically important difference in VAS pain score for acute pain is reported to be around 1.3cm (Kelly AM. Emerg Meg J 2001;18:205-7).</p><p><br></p><p>From a clinical efficacy perspective, the Committee considered the formulations appear to be comparable. Members considered from a safety perspective, any potential change in formulation may lead to alterations in protein folding and the potential for a change in antigenicity. Results from the randomised and open label extension trial regarding efficacy and safety suggest that levels of antibody formation are similar between the formulations.</p><p><br></p><p>The Committee noted the sample pen devices provided to members to assess raised no concerns regarding the redesigned pen device. The Committee considered that there may be some advantages in reduced pain and ease of use with the new formulation and device, particularly for those patients that have underlying chronic pain that may contribute to pain experienced with the injection. However, Members noted the broader significance in terms of impact on quality of life and adherence has not been explored.</p><p><br></p><p>The Committee considered there would be no issues with having both formulations on the market at the same time as all presentations are for single dose use and there would be minimal opportunity to mix these up. Members noted some additional training requirements may be necessary to support patients.</p><p><br></p><p>The Committee considered that overall there may be some small benefits from the new formulation and device for some patients, however this should not be a cost to the Pharmaceutical Budget. Members considered the impacts in terms of future costs related to patent extension and impact on the introduction of adalimumab biosimilars to the New Zealand market should be considered in any funding decision to list the new formulation of adalimumab.</p>', 'fs': '<p>The Committee noted that adalimumab 10 mg, 20 mg and 40 mg subcutaneous presentations are currently listed on Pharmaceutical Schedule, subject to a Special Authority for a range of conditions. The Committee noted that some patients experience significant pain associated with the subcutaneous injection of adalimumab with the currently listed product, however these patients are receiving treatment for chronic conditions that are associated with ongoing pain and the benefit of treatment would usually outweigh the short-term injection related pain.</p><p><br></p><p>Members noted that adalimumab appears to be a more painful injection than etanercept, however only a small number of patients report that injection associated pain was the reason they switched to another injectable biologic (Navarro-Millán et al. PLoS ONE 2016;11(3):e0149781).</p><p><br></p><p>The Committee noted that the new presentation incorporates a two-fold change to the presentation of adalimumab (Humira) to create a citrate-free (CF) formulation, in order to reduce the injection volume, and changes the auto-injector pen device and needle size to aid administration. The current formulation and device could remain available until 30 June 2019 (the end of AbbVie’s current subsidy and delisting protection), although it would be the supplier’s preference to replace the current product sooner. Members noted there may be a potential stock risk in the future if New Zealand continues to list a product that is different to other countries and that PHARMAC staff would need to assess this risk.</p><p><br></p><p>The Committee noted the supplier submitted a new medicine application to Medsafe for the new 40 mg/0.4 ml formulation in March 2016 and registration is expected by May 2017. Members noted that registration of the 10 mg and 20 mg products is not expected until the end of 2018 and these strengths would continue to be available as pre-filled syringes only.</p><p><br></p><p>The Committee noted weak evidence that citrate buffers may be associated with increased pain on subcutaneous injection in comparison with alternatives such as histidine buffer or normal saline (Larsen et al. Basic &amp; Clinical Pharmacology &amp; Toxicology 2006; 98:218–21).\xa0</p><p><br></p><p>Members noted increased injection volume is also associated with increased pain. However, Members considered both concentrations of adalimumab are in a relatively small volume (0.4 ml and 0.8ml). A study by Heise et al. (Diabetes, Obesity and Metabolism 2014;16:971–6) suggested that there may be little difference in pain on injection of either 0.4 or 0.8 ml volume. The Committee considered that it is unclear if a change in needle gauge from 29 to 27 would significantly affect pain on injection.</p><p><br></p><p>The Committee noted four studies provided in the application regarding pain on injection (M10-867, M11-964, M12-783, and M12-159). Two studies were relatively large Phase I trials (M10-867, M12-159) where pre-filled syringes were used to administer a single dose of one of the formulations to healthy subjects. Members noted the Visual Analogue Scale (VAS) scores immediately after injection were statistically significantly higher in the users of the original formulation. However, there was significant variation between subjects as indicated by a very large standard deviation in the numeric results. Pain had diminished significantly by 15 minutes in both treatment arms. Results for both Phase I studies were similar. </p><p><br></p><p>Members noted that two Phase II trials (M11-964 and M12-783) evaluated injection pain following use of a pre-filled syringe of either the current or high-concentration formulation, in treatment naïve and pain experienced patients who had received at least 6 consecutive adalimumab doses prior to screening. Members noted that a recently published paper (Nash et al. Rheumatol Ther August 2016, published online DOI 10.1007/s40744-016-0041-3) provides more detail regarding the VAS scores and shows a statistical difference in VAS immediately after injection between the two formulations. Of note, there is a large numerical difference in scores between the two studies. However, the authors have no explanation for this. Members noted that 67% of patients in the pooled population experienced greater than or equal to 1.3cm less pain following receipt of the 40mg/0.4ml versus the 40mg/0.8ml formulation (p&lt;0.001) and the mean difference in immediate pain after injection for the pooled population was -2.48 (95% CI -2.97 to -2.00; p&lt;0.001). Members noted the minimum clinically important difference in VAS pain score for acute pain is reported to be around 1.3cm (Kelly AM. Emerg Meg J 2001;18:205-7).</p><p><br></p><p>From a clinical efficacy perspective, the Committee considered the formulations appear to be comparable. Members considered from a safety perspective, any potential change in formulation may lead to alterations in protein folding and the potential for a change in antigenicity. Results from the randomised and open label extension trial regarding efficacy and safety suggest that levels of antibody formation are similar between the formulations.</p><p><br></p><p>The Committee noted the sample pen devices provided to members to assess raised no concerns regarding the redesigned pen device. The Committee considered that there may be some advantages in reduced pain and ease of use with the new formulation and device, particularly for those patients that have underlying chronic pain that may contribute to pain experienced with the injection. However, Members noted the broader significance in terms of impact on quality of life and adherence has not been explored.</p><p><br></p><p>The Committee considered there would be no issues with having both formulations on the market at the same time as all presentations are for single dose use and there would be minimal opportunity to mix these up. Members noted some additional training requirements may be necessary to support patients.</p><p><br></p><p>The Committee considered that overall there may be some small benefits from the new formulation and device for some patients, however this should not be a cost to the Pharmaceutical Budget. Members considered the impacts in terms of future costs related to patent extension and impact on the introduction of adalimumab biosimilars to the New Zealand market should be considered in any funding decision to list the new formulation of adalimumab.</p>', 'change': None}, 'Published_Application': {'s': '<p>The Committee reviewed an application from AbbVie for the funding of a new formulation of adalimumab citrate-free and new pen device for all indications to replace the existing presentations of Humira 40mg/0.8ml in a pre-filled syringe and auto-injector.\xa0</p>', 'fs': '<p>The Committee reviewed an application from AbbVie for the funding of a new formulation of adalimumab citrate-free and new pen device for all indications to replace the existing presentations of Humira 40mg/0.8ml in a pre-filled syringe and auto-injector.\xa0</p>', 'change': None}, 'PTAC_Comments': {'s': None, 'fs': None, 'change': None}, 'Outcome': {'s': None, 'fs': None, 'change': None}, 'Links': {'s': '<p>https://pharmac.govt.nz/assets/2016-11-PTAC-minutes.pdf</p>', 'fs': '<p>https://pharmac.govt.nz/assets/2016-11-PTAC-minutes.pdf</p>', 'change': None}, 'Formatted_Date': {'s': 'Nov 2016', 'fs': 'Nov 2016', 'change': None}, 'Event_Description': {'s': None, 'fs': None, 'change': None}, 'e': {'attributes': {'type': 'Application_Event__c', 'url': '/services/data/v65.0/sobjects/Application_Event__c/a0POZ00000Ogl9b2AB'}, 'Id': 'a0POZ00000Ogl9b2AB', 'Event_Date__c': '2016-11-03', 'Stage__c': 'Seeking Clinical Advice', 'Links__c': '<p>https://pharmac.govt.nz/assets/2016-11-PTAC-minutes.pdf</p>', 'Formatted_Date__c': 'Nov 2016', 'Published_Recommendation__c': '<p>The Committee recommended the new formulation and device of adalimumab be listed on the Pharmaceutical Schedule if cost-neutral to the existing presentations of adalimumab, including the future costs of adalimumab with regards to patent extension and the introduction of biosimilar presentations.</p><p><br></p><p>The Committee took into account, where applicable, PHARMAC&#39;s relevant decision-making framework for these recommendations.</p>', 'Published_Application__c': '<p>The Committee reviewed an application from AbbVie for the funding of a new formulation of adalimumab citrate-free and new pen device for all indications to replace the existing presentations of Humira 40mg/0.8ml in a pre-filled syringe and auto-injector.\xa0</p>', 'Published_Discussion__c': '<p>The Committee noted that adalimumab 10 mg, 20 mg and 40 mg subcutaneous presentations are currently listed on Pharmaceutical Schedule, subject to a Special Authority for a range of conditions. The Committee noted that some patients experience significant pain associated with the subcutaneous injection of adalimumab with the currently listed product, however these patients are receiving treatment for chronic conditions that are associated with ongoing pain and the benefit of treatment would usually outweigh the short-term injection related pain.</p><p><br></p><p>Members noted that adalimumab appears to be a more painful injection than etanercept, however only a small number of patients report that injection associated pain was the reason they switched to another injectable biologic (Navarro-Millán et al. PLoS ONE 2016;11(3):e0149781).</p><p><br></p><p>The Committee noted that the new presentation incorporates a two-fold change to the presentation of adalimumab (Humira) to create a citrate-free (CF) formulation, in order to reduce the injection volume, and changes the auto-injector pen device and needle size to aid administration. The current formulation and device could remain available until 30 June 2019 (the end of AbbVie’s current subsidy and delisting protection), although it would be the supplier’s preference to replace the current product sooner. Members noted there may be a potential stock risk in the future if New Zealand continues to list a product that is different to other countries and that PHARMAC staff would need to assess this risk.</p><p><br></p><p>The Committee noted the supplier submitted a new medicine application to Medsafe for the new 40 mg/0.4 ml formulation in March 2016 and registration is expected by May 2017. Members noted that registration of the 10 mg and 20 mg products is not expected until the end of 2018 and these strengths would continue to be available as pre-filled syringes only.</p><p><br></p><p>The Committee noted weak evidence that citrate buffers may be associated with increased pain on subcutaneous injection in comparison with alternatives such as histidine buffer or normal saline (Larsen et al. Basic &amp; Clinical Pharmacology &amp; Toxicology 2006; 98:218–21).\xa0</p><p><br></p><p>Members noted increased injection volume is also associated with increased pain. However, Members considered both concentrations of adalimumab are in a relatively small volume (0.4 ml and 0.8ml). A study by Heise et al. (Diabetes, Obesity and Metabolism 2014;16:971–6) suggested that there may be little difference in pain on injection of either 0.4 or 0.8 ml volume. The Committee considered that it is unclear if a change in needle gauge from 29 to 27 would significantly affect pain on injection.</p><p><br></p><p>The Committee noted four studies provided in the application regarding pain on injection (M10-867, M11-964, M12-783, and M12-159). Two studies were relatively large Phase I trials (M10-867, M12-159) where pre-filled syringes were used to administer a single dose of one of the formulations to healthy subjects. Members noted the Visual Analogue Scale (VAS) scores immediately after injection were statistically significantly higher in the users of the original formulation. However, there was significant variation between subjects as indicated by a very large standard deviation in the numeric results. Pain had diminished significantly by 15 minutes in both treatment arms. Results for both Phase I studies were similar. </p><p><br></p><p>Members noted that two Phase II trials (M11-964 and M12-783) evaluated injection pain following use of a pre-filled syringe of either the current or high-concentration formulation, in treatment naïve and pain experienced patients who had received at least 6 consecutive adalimumab doses prior to screening. Members noted that a recently published paper (Nash et al. Rheumatol Ther August 2016, published online DOI 10.1007/s40744-016-0041-3) provides more detail regarding the VAS scores and shows a statistical difference in VAS immediately after injection between the two formulations. Of note, there is a large numerical difference in scores between the two studies. However, the authors have no explanation for this. Members noted that 67% of patients in the pooled population experienced greater than or equal to 1.3cm less pain following receipt of the 40mg/0.4ml versus the 40mg/0.8ml formulation (p&lt;0.001) and the mean difference in immediate pain after injection for the pooled population was -2.48 (95% CI -2.97 to -2.00; p&lt;0.001). Members noted the minimum clinically important difference in VAS pain score for acute pain is reported to be around 1.3cm (Kelly AM. Emerg Meg J 2001;18:205-7).</p><p><br></p><p>From a clinical efficacy perspective, the Committee considered the formulations appear to be comparable. Members considered from a safety perspective, any potential change in formulation may lead to alterations in protein folding and the potential for a change in antigenicity. Results from the randomised and open label extension trial regarding efficacy and safety suggest that levels of antibody formation are similar between the formulations.</p><p><br></p><p>The Committee noted the sample pen devices provided to members to assess raised no concerns regarding the redesigned pen device. The Committee considered that there may be some advantages in reduced pain and ease of use with the new formulation and device, particularly for those patients that have underlying chronic pain that may contribute to pain experienced with the injection. However, Members noted the broader significance in terms of impact on quality of life and adherence has not been explored.</p><p><br></p><p>The Committee considered there would be no issues with having both formulations on the market at the same time as all presentations are for single dose use and there would be minimal opportunity to mix these up. Members noted some additional training requirements may be necessary to support patients.</p><p><br></p><p>The Committee considered that overall there may be some small benefits from the new formulation and device for some patients, however this should not be a cost to the Pharmaceutical Budget. Members considered the impacts in terms of future costs related to patent extension and impact on the introduction of adalimumab biosimilars to the New Zealand market should be considered in any funding decision to list the new formulation of adalimumab.</p>', 'Status_History__c': 'a132P000000ArCwQAK'}, 'change': None}

 83%|████████▎ | 1674/2015 [00:06<00:01, 280.56it/s]

{'Summary': {'s': None, 'fs': None, 'change': None}, 'Published_Recommendation': {'s': None, 'fs': None, 'change': None}, 'Published_Discussion': {'s': None, 'fs': None, 'change': None}, 'Published_Application': {'s': None, 'fs': None, 'change': None}, 'PTAC_Comments': {'s': None, 'fs': None, 'change': None}, 'Outcome': {'s': None, 'fs': None, 'change': None}, 'Links': {'s': None, 'fs': None, 'change': None}, 'Formatted_Date': {'s': 'Oct 2017', 'fs': 'Oct 2017', 'change': None}, 'Event_Description': {'s': None, 'fs': None, 'change': None}, 'e': {'attributes': {'type': 'Application_Event__c', 'url': '/services/data/v65.0/sobjects/Application_Event__c/a0POZ0000032tQR2AY'}, 'Id': 'a0POZ0000032tQR2AY', 'Event_Date__c': '2017-10-12', 'Stage__c': 'Options Compared', 'Formatted_Date__c': 'Oct 2017', 'Status_History__c': 'a132P000000ArLkQAK'}, 'change': None}

df.describe()

df.Therapeutic_group__c.value_counts().head(20)

Therapeutic_group__c
Oncology Agents and Immunosuppressants                              431
Nervous System                                                      250
Alimentary Tract and Metabolism                                     181
Infections - Agents for Systemic Use                                162
Blood and Blood Forming Organs                                      100
Dermatologicals                                                      98
Cardiovascular System                                                92
Special Foods                                                        89
Respiratory System and Allergies                                     85
National Immunisation Schedule                                       84
Musculoskeletal System                                               76
Hormone Preparations - Systemic Excluding Contraceptive Hormones     53
Genito-Urinary System                                                51
Sensory Organs                                                       50
Various                                                              15
Extemporaneous Compounds                                              8
Name: count, dtype: int64

df.Applicants__c.value_counts().head(20)

Applicants__c
Clinician                               495
PHARMAC Initiated                       385
Subcommittee recommendation              57
Roche                                    47
Consumer                                 45
Novartis                                 42
Merck Sharp & Dohme                      40
Janssen                                  38
NPPA                                     32
AstraZeneca                              31
Nutricia                                 29
Pharmac Initiated                        24
GLAXOSMITHKLINE NZ LIMITED               23
Pfizer                                   23
ROCHE PRODUCTS (NEW ZEALAND) LIMITED     22
GlaxoSmithKline                          21
ABBVIE LIMITED                           20
Gilead Sciences                          20
Boehringer Ingelheim                     19
ASTRAZENECA LIMITED                      18
Name: count, dtype: int64

df.Stage__c.value_counts().plot.bar()

df.to_excel("Pharmac applications.xlsx", index=False)

df["Last Update date"].groupby(df["Last Update date"].dt.to_period("M").astype(str)).count().plot(title="Number of applications last updated per month").data[0]

Scatter({
    'hovertemplate': 'variable=Last Update date<br>index=%{x}<br>value=%{y}<extra></extra>',
    'legendgroup': 'Last Update date',
    'line': {'color': '#636efa', 'dash': 'solid'},
    'marker': {'symbol': 'circle'},
    'mode': 'lines',
    'name': 'Last Update date',
    'orientation': 'v',
    'showlegend': True,
    'x': array(['1995-10', '1998-06', '1998-11', ..., '2025-12', '2026-01', '2026-02'],
               dtype=object),
    'xaxis': 'x',
    'y': array([ 1,  1,  1, ..., 24, 28, 14]),
    'yaxis': 'y'
})

fig = df["Application Received date"].groupby(df["Application Received date"].dt.to_period("M").astype(str)).count().plot(title="Number of applications received per month")
fig.add_trace(df["Last Update date"].groupby(df["Last Update date"].dt.to_period("M").astype(str)).count().plot(title="Number of applications last updated per month").update_traces(line_color='magenta').data[0])

df["Application Received date"].value_counts()

Application Received date
2011-01-01    276
2012-05-01     27
2014-08-01     21
2013-11-01     20
2010-03-01     18
             ... 
2016-11-08      1
2016-11-07      1
2016-11-01      1
2016-10-18      1
2026-01-14      1
Name: count, Length: 790, dtype: int64

df["Decision dates"].dropna().str.replace("Declined", "declined").str.replace("Approved", "approved").str.split("\r\n").apply(lambda x: x[-1].split(":")[1]).value_counts()

Decision dates
The funding application has been approved.        871
The funding application has been declined.        595
The funding application has been .                 11
The funding application has been out of scope.      3
The funding application is closed.                  1
Name: count, dtype: int64

all_events = []
for i, row in tqdm(df.iterrows(), total=len(df)):
    events = pd.read_json(f"applications/{row.Id}.json").dropna()
    events["id"] = row.Id
    all_events.append(events)
events = pd.concat(all_events).reset_index()
events

100%|██████████| 2015/2015 [00:04<00:00, 450.46it/s]

events["date"] = pd.to_datetime(events.dateString, errors="coerce")
events["month"] = events.date.dt.to_period("M")
events["month"]

/tmp/ipykernel_997791/3089976863.py:1: UserWarning:

Could not infer format, so each element will be parsed individually, falling back to `dateutil`. To ensure parsing is consistent and as-expected, please specify a format.

0        1994-04
1        1994-04
2        1994-12
3        1994-09
4        1995-10
          ...   
11054    2026-01
11055    2025-12
11056    2026-01
11057    2026-01
11058    2026-02
Name: month, Length: 11059, dtype: period[M]

events.name.update(events[events.name == "Decision"].events.apply(lambda e: "Approved" if "approved" in e[0]["e"]["Event_Description__c"].lower() else "Declined"))
events.name.value_counts()

/tmp/ipykernel_997791/2827480615.py:1: FutureWarning:

A value is trying to be set on a copy of a DataFrame or Series through chained assignment using an inplace method.
The behavior will change in pandas 3.0. This inplace method will never work because the intermediate object on which we are setting values always behaves as a copy.

For example, when doing 'df[col].method(value, inplace=True)', try using 'df.method({col: value}, inplace=True)' or df[col] = df[col].method(value) instead, to perform the operation inplace on the original object.

name
Application Received               2014
Seeking Clinical Advice            1945
Options Compared                   1551
Under Assessment                   1549
Under Consultation                 1398
Reviewing Consultation Feedback    1121
Approved                            871
Declined                            610
Name: count, dtype: int64

by_month = []
changing_by_month = []
for month in pd.date_range(events.date.min(), events.date.max(), freq="ME"):
    counts = events[events.month <= month.to_period("M")].groupby("id").last().name.value_counts()
    by_month.append(counts)
    counts = events[events.month == month.to_period("M")].groupby("id").last().name.value_counts()
    changing_by_month.append(counts)
by_month = pd.DataFrame(by_month, index=pd.date_range(events.date.min(), events.date.max(), freq="ME").to_period("M").astype(str))
by_month.plot(title="Number of Pharmac applications in each stage by month").show()
by_month.plot.bar(title="Number of Pharmac applications in each stage by month").show()

changing_by_month = pd.DataFrame(changing_by_month, index=pd.date_range(events.date.min(), events.date.max(), freq="ME").to_period("M").astype(str))
changing_by_month.plot.bar(title="Number of Pharmac applications changing to each stage by month").show()

ids = df.Id[df.Therapeutic_group__c == "Oncology Agents and Immunosuppressants"]
by_month = []
changing_by_month = []
for month in pd.date_range(events.date.min(), events.date.max(), freq="ME"):
    counts = events[(events.month <= month.to_period("M")) & (events.id.isin(ids))].groupby("id").last().name.value_counts()
    by_month.append(counts)
    counts = events[(events.month == month.to_period("M")) & (events.id.isin(ids))].groupby("id").last().name.value_counts()
    changing_by_month.append(counts)
by_month = pd.DataFrame(by_month, index=pd.date_range(events.date.min(), events.date.max(), freq="ME").to_period("M").astype(str))
by_month.plot(title="Number of Oncology Agents and Immunosuppressants Pharmac applications in each stage by month").show()

changing_by_month = pd.DataFrame(changing_by_month, index=pd.date_range(events.date.min(), events.date.max(), freq="ME").to_period("M").astype(str))
changing_by_month.plot.bar(title="Number of Oncology Agents and Immunosuppressants Pharmac applications changing to each stage by month").show()

	Id	Name	Applications__c	Brand_Name__c	Chemical_Name__c	Applicants__c	Funding_requested_for__c	Stage__c	Pharmaceutical__c	Community_URL__c	Therapeutic_group__c
0	a0ROZ000009J5Ev2AK	15-valent pneumococcal conjugate vaccine (PCV15)	A-04423	VAXNEUVANCE.	15-valent pneumococcal conjugate vaccine (PCV15)	MERCK SHARP & DOHME (NEW ZEALAND) LIMITED	Prevention of invasive pneumococcal disease	Decision	15-valent pneumococcal conjugate vaccine (PCV1...	https://connect.pharmac.govt.nz/apptracker/s/a...	NaN
1	a0ROZ000004CX2l2AG	Adjuvanted inactivated quadrivalent influenza ...	A-03341	FLUAD® QUAD	Adjuvanted inactivated quadrivalent influenza ...	Seqirus	influenza vaccination for people aged 65 years...	Decision	Adjuvanted inactivated quadrivalent influenza ...	https://connect.pharmac.govt.nz/apptracker/s/a...	National Immunisation Schedule
2	a0ROZ00000Cn1xE2AR	Adjuvanted inactivated trivalent influenza vac...	A-00724	Fluad	Adjuvanted inactivated trivalent influenza vac...	Seqirus	Influenza vaccine for people 65 years of age a...	Options Compared	Adjuvanted inactivated trivalent influenza vac...	https://connect.pharmac.govt.nz/apptracker/s/a...	National Immunisation Schedule
3	a0R2P000000gVYDUA2	Bevacizumab and Human Papillomavirus (HPV) vac...	A-00655	NaN	Bevacizumab and Human Papillomavirus (HPV) vac...	PHARMAC Initiated	Recurrent respiratory papillomatosis	Decision	Bevacizumab and Human Papillomavirus (HPV) vac...	https://connect.pharmac.govt.nz/apptracker/s/a...	Respiratory System and Allergies
4	a0R2P000000LmcWUAS	Diphtheria and tetanus vaccine	A-00221	NaN	Diphtheria and tetanus vaccine	PHARMAC Initiated	Widening of access	Decision	Diphtheria and tetanus vaccine	https://connect.pharmac.govt.nz/apptracker/s/a...	National Immunisation Schedule
...	...	...	...	...	...	...	...	...	...	...	...
2010	a0ROZ00000083aG2AQ	AEON Sodium Chloride 5 Percent	A-04432	AEON	AEON Sodium Chloride 5 Percent	MEDIX 21 LIMITED	Corneal oedema relief	Seeking Clinical Advice	AEON Sodium Chloride 5 Percent (AEON)	https://connect.pharmac.govt.nz/apptracker/s/a...	NaN
2011	a0ROZ00000DqVYD2A3	Pegunigalsidase alfa-iwxj	A-05325	ELFABRIO	Pegunigalsidase alfa-iwxj	CHIESI NEW ZEALAND LIMITED	Fabry Disease	Options Compared	Pegunigalsidase alfa-iwxj (ELFABRIO)	https://connect.pharmac.govt.nz/apptracker/s/a...	NaN
2012	a0ROZ000003nufF2AQ	Elemental Food (Elemental Gold)	A-04296	It is not a pharmaceutical. The brand name is ...	Elemental Food (Elemental Gold)	ENDOTHERAPEUTICS NZ LIMITED	Currently funded indications	Seeking Clinical Advice	Elemental Food (Elemental Gold) (It is not a p...	https://connect.pharmac.govt.nz/apptracker/s/a...	NaN
2013	a0ROZ00000AQkoE2AT	SARS-CoV-2 rS (Omicron XBB.1.5)	A-04785	NUVAXOVID XBB.1.5	SARS-CoV-2 rS (Omicron XBB.1.5)	BIOCELECT NEW ZEALAND LIMITED	prevention of COVID-19	Options Compared	SARS-CoV-2 rS (Omicron XBB.1.5) (NUVAXOVID XBB...	https://connect.pharmac.govt.nz/apptracker/s/a...	NaN
2014	a0ROZ0000070NGj2AM	Elasomeran, Elasomeran and Davesomeran, Anduso...	A-04863	SPIKEVAX	Elasomeran, Elasomeran and Davesomeran, Anduso...	Moderna Australia Pty Ltd	active immunisation to prevent coronavirus dis...	Under Assessment	Elasomeran, Elasomeran and Davesomeran, Anduso...	https://connect.pharmac.govt.nz/apptracker/s/a...	NaN

	Id	Name	Applications__c	Brand_Name__c	Chemical_Name__c	Applicants__c	Funding_requested_for__c	Stage__c	Pharmaceutical__c	Community_URL__c	Therapeutic_group__c	Application Received date	Last Update date	Days elapsed between application and last update	Days until Seeking Clinical Advice	Days until Under Assessment	Days until Options Compared	Days until Under Consultation	Days until Reviewing Consultation Feedback	Days until Decision	Application Received dates	Seeking Clinical Advice dates	Under Assessment dates	Options Compared dates	Under Consultation dates	Reviewing Consultation Feedback dates	Decision dates
688	a0R2P000000LmkWUAS	Risperidone tablets	A-01127	Risperdal	Risperidone tablets	Janssen	Schizophrenia	Decision	Risperidone tablets (Risperdal)	https://connect.pharmac.govt.nz/apptracker/s/a...	Nervous System	1994-04-01	1995-10-01	548	0 days	244 days	-91 days	NaT	NaT	395 days	1994-04-01:Application received	1994-04-01:Clinical advice required\r\n1994-06...	1994-12-01:Working to compare options\r\n1995-...	1994-09-01:The relative ranking of the pharmac...	NaN	NaN	1995-10-01:The funding application has been Ap...
584	a0R2P000000LmjmUAC	Gabapentin	A-01197	Neurontin	Gabapentin	Parke Davis	Partial seizures in patients who have not achi...	Decision	Gabapentin (Neurontin)	https://connect.pharmac.govt.nz/apptracker/s/a...	Nervous System	1994-08-01	2001-03-01	2404	184 days	28 days	61 days	2072 days	NaT	59 days	1994-08-01:Application received	1995-02-01:Clinical advice required\r\n1995-03...	1995-03-01:Working to compare options	1995-05-01:The relative ranking of the pharmac...	2001-01-01:Public consultation for this applic...	NaN	2001-03-01:The funding application has been Ap...
982	a0R2P000000LmThUAK	Somatropin - Growth Hormone	A-01165	Genotropin	Somatropin - Growth Hormone	Clinician	Adult and adolescent patients with growth ho...	Decision	Somatropin - Growth Hormone (Genotropin)	https://connect.pharmac.govt.nz/apptracker/s/a...	Hormone Preparations - Systemic Excluding Cont...	1995-09-01	2005-09-01	3653	0 days	427 days	-366 days	5083 days	NaT	-1491 days	1995-09-01:Application received	1995-09-01:Clinical advice required\r\n1995-11...	1996-11-01:Working to compare options	1995-11-01:The relative ranking of the pharmac...	2009-10-01:Public consultation for this applic...	NaN	2005-09-01:The funding application has been Ap...
593	a0R2P000000Lmo2UAC	Interferon beta-1-beta	A-01183	Betaferon	Interferon beta-1-beta	Bayer	Relapsing remitting multiple sclerosis	Decision	Interferon beta-1-beta (Betaferon)	https://connect.pharmac.govt.nz/apptracker/s/a...	Nervous System	1996-01-01	1999-07-01	1277	0 days	NaT	1216 days	0 days	NaT	61 days	1996-01-01:Application received	1996-01-01:Clinical advice required\r\n1996-03...	NaN	1999-05-01:The relative ranking of the pharmac...	1999-05-01:Public consultation for this applic...	NaN	1999-07-01:The funding application has been Ap...
1407	a0R2P000000LmqWUAS	Anastrozole	A-01169	Arimidex	Anastrozole	AstraZeneca	Third line treatment of advanced breast cancer	Decision	Anastrozole (Arimidex)	https://connect.pharmac.govt.nz/apptracker/s/a...	Oncology Agents and Immunosuppressants	1997-02-01	1998-12-01	668	0 days	89 days	518 days	0 days	NaT	61 days	1997-02-01:Application received	1997-02-01:Clinical advice required\r\n1997-05...	1997-05-01:Working to compare options	1998-10-01:The relative ranking of the pharmac...	1998-10-01:Public consultation for this applic...	NaN	1998-12-01:The funding application has been Ap...
...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...
1282	a0ROZ00000Dms532AB	Riociguat	A-05544	ADEMPAS	Riociguat	Clinician	Chronic Thromboembolic Pulmonary Hypertension ...	Seeking Clinical Advice	Riociguat (ADEMPAS)	https://connect.pharmac.govt.nz/apptracker/s/a...	NaN	2025-10-28	2026-02-02	97	123 days	NaT	NaT	NaT	NaT	NaT	2025-10-28:Application received	2026-02-02:Clinical advice required	NaN	NaN	NaN	NaN	NaN
1770	a0ROZ00000DL1uT2AT	Mepolizumab	A-05540	Nucala	Mepolizumab	GLAXOSMITHKLINE NZ LIMITED	Inadequately controlled chronic obstructive pu...	Seeking Clinical Advice	Mepolizumab (Nucala)	https://connect.pharmac.govt.nz/apptracker/s/a...	Respiratory System and Allergies	2025-10-31	2026-01-09	70	92 days	NaT	NaT	NaT	NaT	NaT	2025-10-31:Application received	2026-01-09:Clinical advice required	NaN	NaN	NaN	NaN	NaN
1841	a0ROZ00000DGeA52AL	Upadacitinib	A-05543	Rinvoq	Upadacitinib	ABBVIE LIMITED	Giant cell ateritis (GCA), glucocorticoid tape...	Seeking Clinical Advice	Upadacitinib (Rinvoq)	https://connect.pharmac.govt.nz/apptracker/s/a...	Musculoskeletal System	2025-10-31	2026-01-05	66	92 days	NaT	NaT	NaT	NaT	NaT	2025-10-31:Application received	2026-01-05:Clinical advice required	NaN	NaN	NaN	NaN	NaN
1919	a0ROZ00000DKizt2AD	pembrolizumab	A-05472	KEYTRUDA	pembrolizumab	MERCK SHARP & DOHME (NEW ZEALAND) LIMITED	Squamous Cell Carcinoma of the Head and Neck, ...	Seeking Clinical Advice	pembrolizumab (KEYTRUDA)	https://connect.pharmac.govt.nz/apptracker/s/a...	NaN	2025-12-19	2026-01-09	21	31 days	NaT	NaT	NaT	NaT	NaT	2025-12-19:Application received	2026-01-09:Clinical advice required	NaN	NaN	NaN	NaN	NaN
1126	a0ROZ00000DoZ9Z2AV	Emicizumab	A-05466	Hemlibra	Emicizumab	Clinician	Haemophilia A, moderate severity, severe bleed...	Seeking Clinical Advice	Emicizumab (Hemlibra)	https://connect.pharmac.govt.nz/apptracker/s/a...	NaN	2026-01-14	2026-02-03	20	31 days	NaT	NaT	NaT	NaT	NaT	2026-01-14:Application received	2026-02-03:Clinical advice required	NaN	NaN	NaN	NaN	NaN

	Application Received date	Last Update date	Days elapsed between application and last update	Days until Seeking Clinical Advice	Days until Under Assessment	Days until Options Compared	Days until Under Consultation	Days until Reviewing Consultation Feedback	Days until Decision
count	2015	2015	2015.000000	1944	1549	1551	1398	1120	1480
mean	2014-05-26 13:35:24.267990016	2018-03-16 14:57:35.285359872	1390.057072	140 days 12:11:06.666666666	424 days 09:19:38.308586184	296 days 00:48:16.711798840	783 days 18:53:02.832618024	66 days 14:38:08.571428571	156 days 07:05:11.351351352
min	1994-04-01 00:00:00	1995-10-01 00:00:00	-94.000000	-2557 days +00:00:00	-2162 days +00:00:00	-6087 days +00:00:00	-6270 days +00:00:00	-671 days +00:00:00	-7215 days +00:00:00
25%	2011-01-01 00:00:00	2013-04-24 00:00:00	485.000000	0 days 00:00:00	28 days 00:00:00	0 days 00:00:00	31 days 00:00:00	28 days 00:00:00	31 days 00:00:00
50%	2013-12-02 00:00:00	2019-07-11 00:00:00	866.000000	61 days 00:00:00	213 days 00:00:00	122 days 00:00:00	334 days 00:00:00	30 days 00:00:00	61 days 00:00:00
75%	2019-04-07 12:00:00	2024-03-29 00:00:00	1844.500000	181 days 00:00:00	427 days 00:00:00	396 days 00:00:00	1126 days 00:00:00	31 days 00:00:00	151 days 00:00:00
max	2026-01-14 00:00:00	2026-02-11 00:00:00	9922.000000	4626 days 00:00:00	7946 days 00:00:00	5875 days 00:00:00	7975 days 00:00:00	7184 days 00:00:00	6515 days 00:00:00
std	NaN	NaN	1372.478161	381 days 02:19:44.749732920	836 days 23:06:13.989561008	818 days 06:10:48.919041072	1243 days 22:09:53.186913056	431 days 09:08:11.626936856	681 days 08:41:04.928734328

	text	position	name	last	events	dateString	collapsed	checked
0	<p>New funding applications are referred to on...	0	Application Received	False	[{'Summary': {'s': None, 'fs': None, 'change':...	Aug 2022	False	True
1	<p>Pharmac is identifying and gathering inform...	1	Seeking Clinical Advice	False	[{'Summary': {'s': None, 'fs': None, 'change':...	Sep 2022	False	True
2	<p>Following Clinical Advice, Pharmac staff co...	2	Under Assessment	False	[{'Summary': {'s': None, 'fs': None, 'change':...	Mar 2023	False	True
3	<p>Pharmac staff uses a prioritisation process...	3	Options Compared	False	[{'Summary': {'s': None, 'fs': None, 'change':...	Jun 2024	False	True
4	<p>Pharmac is consulting on a proposal to eith...	4	Under Consultation	False	[{'Summary': {'s': None, 'fs': None, 'change':...	Oct 2024	False	True
5	<p>Following the consultation process, Pharmac...	5	Reviewing Consultation Feedback	False	[{'Summary': {'s': None, 'fs': None, 'change':...	Nov 2024	False	True
6	<p>We refer to our decisions about whether and...	6	Decision	True	[{'Summary': {'s': None, 'fs': None, 'change':...	Jun 2025	False	True